Color vision relies on a detection of distinct wavelengths of light by different rhodopsin molecules present in photoreceptor cells (PR's). To avoid sensory overlap, most visual systems have developed a mechanism to allow just one rhodopsin (Rh) to be expressed per PR. Recent evidence has suggested that the regulation of rh gene expression is purely transcriptional, requiring the combination of a site for PR identity together with subtype specificity elements. Pax-6 recently been shown to be important for PR identity through an element common to all rh genes. Furthermore, preliminary data indicates that the transcription factor orthodenticle (otd) is important for subtype-specific expression of rh3, rh5, and rh6. However, most of the transcription factors responsible for PR subtype specificity have not yet been described. Therefore, the studies described in this proposal are focused on identifying and characterizing the transcription factors involved in rh gene expression. To achieve these goals, we will address three specific aims: 1) characterize the role of Pax-6 in PR-specific rh gene expression; 2) characterize the role of otd in subtype- specific rh gene expression; and 3) identify novel transcription factors involved in subtype-specific gene expression. These experiments will be performed using a variety of molecular and genetic approaches. The successful completion of this work will lead to a better understanding of the regulation of the rhodopsin family of proteins necessary for color vision in the Drosophila compound eye. Interestingly, the vertebrate homologs of both Pax-6 and otd have been associated with retina-specific gene expression, and mutations in these gene products result in eye- specific diseases such as aniridia and cone-rod dystrophy. Therefore, studies derived from this work may also provide insight into the mechanisms underlying patterning of the vertebrate retina.